Issue 18, 2023

A modular aldol approach for internal fluorescent molecular rotor chalcone surrogates for DNA biosensing applications

Abstract

Fluorescent molecular rotors (FMRs) are critical tools for probing nucleic acid structure and function. Many valuable FMRs have been incorporated into oligonucleotides, although the methods of doing so can be cumbersome. Development of synthetically simple, high yielding modular methods to fine-tune dye performance is crucial to expand the biotechnological applications of oligonucleotides. Herein, we report the utility of 6-hydroxy-indanone (6HI) with a glycol backbone to serve as a handle for on-strand aldehyde capture as a modular aldol approach for site-specific insertion of internal FMR chalcones. Aldol reactions with aromatic aldehydes containing N-donors proceed in high yield to create modified DNA oligonucleotides, which in the duplex match the stability of the fully paired canonical B-form with strong stacking interactions between the planar probe and the flanking base pairs, as evidenced by molecular dynamics (MD) simulations. The FMR chalcones possess remarkable quantum yields (Φfl up to 76%) in duplex DNA, coupled with large Stokes shifts (Δν up to 155 nm), light-up emissions (Irel up to 60-fold) that span the visible region (λem 518–680 nm) with brightness up to 17 480 cm−1 M−1. The library also contains a FRET pair and dual emission probes, suitable for ratiometric sensing. The ease of aldol insertion coupled with the excellent performance of the FMR chalcones permits their future wide-spread use.

Graphical abstract: A modular aldol approach for internal fluorescent molecular rotor chalcone surrogates for DNA biosensing applications

Supplementary files

Article information

Article type
Edge Article
Submitted
10 2 2023
Accepted
11 4 2023
First published
11 4 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 4832-4844

A modular aldol approach for internal fluorescent molecular rotor chalcone surrogates for DNA biosensing applications

R. E. Johnson, M. T. Murray, L. J. Bycraft, S. D. Wetmore and R. A. Manderville, Chem. Sci., 2023, 14, 4832 DOI: 10.1039/D3SC00772C

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